The study of the binding of tricyclic antidepressant drugs, imipramine and chlorimpramine to trophozoites of Giardia lamblia was completed this year. Interaction of these drugs with the parasite differs markedly from their interaction with mammalian cells. G. lamblia has a large number of binding sites in contrast to mammalian cells, and the binding kinetics shows very weak binding. There is no evidence for specific binding receptors in the parasite as is present in mammalian cells. This may be a reflection of the primitive position of G. lamblia on the evolutionary tree of eukaryotic cells. Collaborative studies, initiated last year with Dr. Mowatt, examined the biochemical and genetic characteristics of a key glycolytic enzyme triosephosphate isomerase. Initial studies have now localized the enzyme in the soluble (cytosolic) fraction of G. lamblia trophozoites. It appears to be a true soluble enzyme not associated with any glycosomal-like structures as in other parasitic protozoa. Genetic probes and markers for this enzyme are being developed by Dr. Mowatt. Collaborative studies with Dr. Diamond of the respiratory metabolism of Entamoeba confirmed our previous observation that only the reptilian species exhibited a marked stimulatory effect of Mn2+ on NAD(P)H oxidase. This observation may correlate with the distinct differences in molecular taxonomy found among these species of Entamoeba.